Bibliographic details of the publications numerically referred to in this specification are collected at the end of the description.
There is currently no effective method of treating HIV infection. Current treatment strategies can suppress plasma HIV-1 RNA levels to very low levels, however latently infected cells harbouring HIV-1 DNA remain detectable and viral resistance and relapse is common [1,2]. Treatment-induced reductions in HIV-1 levels results in a loss of antigenic stimulus for effective immune responses. HIV-specific cytotoxic T lymphocyte (CTL) responses, thought to be a critical effector mechanism in the control of HIV-1, decline to low levels following effective anti-HIV therapy [3].
Previous trials of therapeutic HIV-1 vaccines have shown that it is possible to stimulate anti-HIV immune responses in HIV-1 infected individuals, but no clinical benefit has been demonstrated [4-6]. Prior studies have used protein-based HIV-1 vaccines incapable of inducing CTL responses or vaccinated individuals with substantial levels of replicating HIV-1. Even moderate levels of replicating HIV-1 results in a loss of HIV-specific CD4+ T-helper (Th) responses which are required to initiate and sustain an effective CTL response [7].
Additionally, no preventative HIV vaccines currently exist. Although simple recombinant avipox vaccines (without co-expression of cytokines) can induce CTL responses in a proportion of human and non-human primate subjects, the response is often weak, transient, or non-existent. There is a need for more reliable vaccine vectors for the induction of HIV specific CTL and Th responses.
In work leading up to the present invention, the inventors have determined that the magnitude and phenotype of the specific immune response to HIV can be enhanced by vaccination with a recombinant fowl pox virus construct comprising both an HIV gag/pol encoding nucleic acid molecule and a cytokine encoding nucleic acid molecule, in particular, IFN-γ.